ライフサイエンスコーパス: dolichol

1 or for cleavage of Glc(3)Man(9)GlcNAc(2)-P-P-dolichol.

2 tic mechanism of the synthesis of GlcNAc-P-P-dolichol.

3 nthetic pathway that produces the LLO anchor dolichol.

4 cNAc-P-P-dolichol but not that of GlcNAc-P-P-dolichol.

5 d by the glycolipid Glc(3)Man(9)GlcNAc(2)-PP-dolichol.

6 D1 overexpression or by supplementation with dolichol.

7 e-derived metabolites, such as ubiquinone or dolichol.

8 All four major dolichol species-dolichol-17 (Dol-17), Dol-18, Dol-19, and Dol-20, increa

9 Retinol, atRA glucuronide, 13-cis-RA, dolichol, 5,6-epoxy-RA, and vitamin D(3) did not compete

10 Man 7GlcNAc 2-PP-dolichol, a higher-order lipid intermediate, was flipped

11 lippase that translocates Man(5)GlcNAc(2)-PP-dolichol, a lipid intermediate of N-glycosylation.

12 and SlCPTBP localize to the ER, the site of dolichol accumulation and synthesis in eukaryotes.

13 by SRD5A3, and the reduction of dolichal to dolichol, again by DHRSX.

14 lyprenols and dolichols, i.e. detection of a dolichol along with significant levels of its precursor

15 GlcNAc-P-P-dolichol also exerts a stimulatory effect on the biosynt

16 , a highly sensitive and specific method for dolichol analysis.

17 atives, concomitant with decreased levels of dolichol and derivatives, but no change in polyprenal le

18 The apparent K(i) values for GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol under basal cond

19 hol; the apparent K(i) values for GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol were 2.2 and 11

20 5 and Lec35 cells accumulate Man5GlcNAc2-P-P-dolichol and glucosaminyl-acylphosphatidylinositol.

21 In an alg11 lesion, both Man(3)GlcNAc(2)-PP-dolichol and Man(4)GlcNAc(2)-PP-dolichol are translocate

22 nthesis of glucose(3)mannose(9)GlcNAc(2)-P-P-dolichol and N-linked glycosylation.

23 CPTL1 and TkCPT4/TkCPTL1 produced long-chain dolichols and polyisoprenes, TkCPT5 and TkCPT6 produced

24 is-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of s

25 ulated both eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol) and bacterial (Glc1-GalNAc5-Bac1-PP-Undecapren

26 nylpyrophosphoryldolichol (GlcNAc-GlcNAc-P-P-dolichol), and product inhibition by GlcNAc-P-P-dolichol

27 GlcNAc(2)-PP-dolichol and Man(4)GlcNAc(2)-PP-dolichol are translocated into the ER lumen as substrate

28 In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more h

29 ess inexpensive phytol instead of the native dolichol as a lipid carrier.

30 ed oligosaccharide (LLO) Glc3Man9GlcNAc2-P-P-dolichol as measured with radioactive sugar precursors.

31 tein has a region homologous to the putative dolichol-binding region in the yeast ALG1 protein, but i

32 s-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein gly

33 Mutations affecting dolichol biosynthesis cause non-syndromic retinal degene

34 s expression in the Saccharomyces cerevisiae dolichol biosynthesis mutant (rer2) complemented the tem

35 ctive cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polypr

36 rther show that the involvement of SlCPT3 in dolichol biosynthesis requires the participation of a di

37 h isoprenoid metabolites being important for dolichol biosynthesis, protein prenylation, and modifica

38 inery yields insights into the regulation of dolichol biosynthesis.

39 tous expressions in lettuce, showed a potent dolichol biosynthetic activity in vitro.

40 k the de novo formation of GlcNAc-GlcNAc-P-P-dolichol but not that of GlcNAc-P-P-dolichol.

41 is occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in t

42 ol-P that was trapped as Glc3Man9GlcNAc2-P-P-dolichol by translation arrest.

43 complex, leading to free glycan release from dolichol carriers, as well as immune activation and auto

44 ates showed that MPD flippase recognizes the dolichol chain of MPD, preferring a saturated alpha-isop

45 A shift in the dolichol chain-length profile with age was also observed

46 ed in the synthesis of sterols, carotenoids, dolichols, coenzyme Q, heme a and farnesylated proteins.

47 e in plant cells which makes manipulation of dolichol content in plant tissues feasible.

48 mily (SlCPT3) resulted in a ~60% decrease in dolichol content.

49 p of the synthesis of the Man(5)GlcNAc(2)-PP-dolichol core oligosaccharide on the cytosolic face of t

50 es the factors mediating the key step of the dolichol cycle in plant cells which makes manipulation o

51 n involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal.

52 nce of an unexpected alternative pathway for dolichol de novo biosynthesis.

53 equired to complement the growth defects and dolichol deficiency of the yeast dolichol mutant, rer2.

54 ects although disturbances in other cellular dolichol-dependent processes could also contribute.

55 Tase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplas

56 All three genes are involved in dolichol-dependent protein glycosylation, a pathway not

57 le for all known classes of monosaccharide-P-dolichol-dependent reactions in mammals.

58 nto the ER lumen as substrates for the Man-P-dolichol-dependent sugar transferases in this compartmen

59 er of a precursor Glc(3)Man(9)GlcNAc(2) from dolichol (Dol) to consensus Asn residues in nascent prot

60 ing of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the

61 Supplementation of the human diet with dolichol-enriched plant tissues could allow new therapeu

62 esolved from the oligosaccharide-diphosphate dolichol flippase that translocates Man(5)GlcNAc(2)-PP-d

63 even though for both cell lines a defect in dolichol formation from polyprenol was previously establ

64 ucose(3)mannose(9)N-acetylglucosamine(2)-P-P-dolichol (G(3)M(9)Gn(2)-P-P-Dol) to asparaginyl residues

65 tion of tryptophanyl residues, and glucose-P-dolichol (GPD)-dependent glucosylation of LLO.

66 smic leaflet or is first dephosphorylated to dolichol has not been determined.

67 on by catalyzing the synthesis of GlcNAc-P-P-dolichol, has multiple transmembrane spans and a catalyt

68 erestingly, co-occurrence of polyprenols and dolichols, i.e. detection of a dolichol along with signi

69 me Q (a component of the respiratory chain), dolichols (important for protein glycosylation), and iso

70 responsible for conversion of polyprenol to dolichol in Arabidopsis thaliana.

71 The presence of residual dolichol in cells depleted for this enzyme suggests the

72 Shortage of dolichol in PPRD2-deficient cells is partially rescued b

73 talyzes the CTP-dependent phosphorylation of dolichol in the biosynthesis de novo and possibly the re

74 lcNAc2-P-P-dolichol to Glc0-3Man9GlcNAc2-P-P-dolichol in vivo.

75 Age-related dolichol increases occurred in two distinct phases: Phas

76 Dolichol is a lipid uniquely important for retinal cells

77 Dolichol is a required cofactor for protein glycosylatio

78 , the discovery of PPs is intriguing because dolichol is a well-established constituent of human neur

79 Synthesis of Glc 3Man 9GlcNAc 2-PP-dolichol is initiated on the cytoplasmic side of the ER

80 The glycolipid Glc 3Man 9GlcNAc 2-PP-dolichol is the oligosaccharide donor for protein N-glyc

81 ucosaminylpyrophosphoryldolichol (GlcNAc-P-P-dolichol), is under investigation as a possible site of

82 in N-glycosylation, Glc(3)Man(9)GlcNAc(2)-PP-dolichol, is synthesized via a multistep pathway that st

83 ichol), and product inhibition by GlcNAc-P-P-dolichol itself.

84 Dolichol kinase (DK) catalyzes the CTP-dependent phospho

85 No changes in dolichol kinase activity were observed.

86 domain that is present in the SEC59-encoded dolichol kinase and CDS1-encoded CDP-diacylglycerol synt

87 zed for lipid intermediate biosynthesis, and dolichol kinase is not required for recycling.

88 5 and slr1652 indicated modest similarity to dolichol kinase.

89 We characterized age-related changes in dolichol levels in the retinas of C57BL/6 mice of both s

90 The age-related increase in dolichol levels may influence the physical properties of

91 icity of the glycosyl donor, three unnatural dolichol-linked disaccharide analogues (Dol-PP-GlcNTFA-G

92 Thus, control of the dolichol-linked Glc(3)Man(9)GlcNAc(2) supply gives the U

93 Inhibition of dolichol-linked Glc(3)Man(9)GlcNAc(2) synthesis by gluco

94 This study reports that conversion of dolichol-linked Man(2-5)GlcNAc(2) intermediates into mat

95 The dolichol-linked monosaccharide Dol-PP-GlcNAc 3 was found

96 to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide

97 t enzyme, near-homogeneous preparations of a dolichol-linked oligosaccharide (Glc(3)Man(9)GlcNAc(2)-P

98 isms by the addition of a second, regulatory dolichol-linked oligosaccharide binding site, the presen

99 ferase (OT), which catalyzes the transfer of dolichol-linked oligosaccharide chains to nascent polype

100 ssembled high-mannose oligosaccharide from a dolichol-linked oligosaccharide donor onto asparagine ac

101 preferentially utilizes the fully assembled dolichol-linked oligosaccharide Glc(3)Man(9)GlcNAc(2)-PP

102 The dolichol-linked oligosaccharide Glc3Man9GlcNAc2-PP-Dol i

103 oligosaccharides as well as a heterogeneous dolichol-linked oligosaccharide library.

104 lum with the synthesis of a highly conserved dolichol-linked oligosaccharide precursor.

105 The second step of dolichol-linked oligosaccharide synthesis in the N-linke

106 he synthesis of GDP-mannose, a substrate for dolichol-linked oligosaccharide synthesis.

107 Mature dolichol-linked oligosaccharides (mDLOs) needed for euka

108 ed donor substrate from a complex mixture of dolichol-linked oligosaccharides (OS-PP-Dol) has not bee

109 production, leading to diminished levels of dolichol-linked oligosaccharides and a broad reduction i

110 es cerevisiae using structurally homogeneous dolichol-linked oligosaccharides as well as a heterogene

111 However, many protist organisms assemble dolichol-linked oligosaccharides that lack glucose resid

112 The patients produced a truncated dolichol-linked precursor oligosaccharide with 5 mannose

113 hol, which is essential for the formation of dolichol-linked precursor oligosaccharides.

114 catalyzes the co-translational transfer of a dolichol-linked tetradecasaccharide (Dol-PP-GlcNAc(2)Man

115 nnose used to make Glc(3)Man(9)GlcNAc(2)-P-P-dolichol (lipid-linked oligosaccharide; LLO).

116 sformed cells that are known to have altered dolichol lipids.

117 of the lipid intermediate Man(5)GlcNAc(2)-PP-dolichol (M5-DLO) across the ER membrane.

118 lipping of the intermediate Man 5GlcNAc 2-PP-dolichol (M5-DLO) across the ER.

119 osynthetic lipid intermediate Man5GlcNAc2-PP-dolichol (M5-DLO) flips from the cytoplasmic to the lumi

120 te the lipid intermediate Man(5)GlcNAc(2)-PP-dolichol (M5-DLO) on the cytoplasmic side of the ER.

121 transbilayer movement of Man(5)GlcNAc(2)-P-P-dolichol (M5-DLO), a series of experiments was conducted

122 f the glycolipid Man(5)GlcNAc(2)-diphosphate dolichol (Man(5)GlcNAc(2)-PP-Dol) across the endoplasmic

123 o observed under conditions where mannosyl-P-dolichol (Man-P-dol) stimulated the biosynthesis of GlcN

124 genital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio

125 in E. coli and used for mannosylation of the dolichol mimic, phytanyl pyrophosphate GlcNAc2.

126 ich is preassembled onto a membrane-anchored dolichol molecule embedded within the endoplasmic reticu

127 Dolichol monophosphate (Dol-P) functions as an obligate

128 r utilization of the mannose donor mannose-P-dolichol (MPD) in synthesis of both lipid-linked oligosa

129 Mannose-phosphate-dolichol (MPD) is a multifunctional glycolipid that is s

130 and utilization, respectively, of mannose-P-dolichol (MPD).

131 defects and dolichol deficiency of the yeast dolichol mutant, rer2.

132 to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) acro

133 al levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units.

134 ent at the ER is also required for efficient dolichol oligosaccharide biosynthesis.

135 ges in concentrations of Glc3Man9GlcNAc2-P-P-dolichol or early LLO intermediates.

136 te of synthesis of [(3)H]Man(9)GlcNAc(2)-P-P-dolichol or Man(9)[(3)H]GlcNAc(2)-P-P-dolichol, respecti

137 nitiation by accumulated Glc3Man9GlcNAc2-P-P-dolichol, or inhibition of a GDP-mannose dependent trans

138 UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT) is an endoplasmi

139 Hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), which initiates

140 three transferases shared a limited pool of dolichol-P that was trapped as Glc3Man9GlcNAc2-P-P-dolic

141 ppears to make available a secondary pool of dolichol-P, masking inhibition by translation arrest, as

142 The GPT mutants had no effect on two other dolichol-P-dependent endoplasmic reticulum enzymes.

143 ll wall beta-1,6-glucan is indirect and that dolichol-P-glucose is not an intermediate in this pathwa

144 nthetic pathway, disappear in the absence of dolichol-P-glucose synthase (alg5Delta).

145 structed a double mutant, alg5Delta (lacking dolichol-P-glucose synthase) cwh41Delta, and found that

146 Except for dolichol-P-mannose, other precursors, including mannose,

147 results directly support the hypothesis that dolichol-P-P-oligosaccharide assembly is initiated in th

148 f GlcNAc-P-P-dolichol, the committed step of dolichol-P-P-oligosaccharide synthesis.

149 hesis depends upon a limited primary pool of dolichol-P.

150 s have enabled identification of most of the dolichol pathway enzymes in Saccharomyces cerevisiae, th

151 he Alg9 and Alg12 proteins, which act in the dolichol pathway for N-glycosylation.

152 Inhibition of the dolichol pathway of protein N-glycosylation also causes

153 which is the only glycosyltransferase in the dolichol pathway that has been expressed as an active pr

154 synthesis, requiring multiple cycles of the dolichol pathway, occurred in the absence of CTP.

155 erved between these two intermediates of the dolichol pathway.

156 inked glycoproteins proceeds by means of the dolichol pathway.

157 le of glycosyltransferases that comprise the dolichol pathway.

158 bound glycosyltransferases that comprise the dolichol pathway.

159 annose in this study, is added to a distinct dolichol phosphate carrier.

160 -83 are modified by a pentasaccharide, while dolichol phosphate is modified by a tetrasaccharide comp

161 Dolichol phosphate mannose (Dol-P-Man), formed upon tran

162 prenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which genera

163 We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a

164 me time, cells grown at low salinity contain dolichol phosphate modified by a distinct tetrasaccharid

165 The gene encoding UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate trans

166 first step of this pathway, the reaction of dolichol phosphate with UDP-GlcNAc to form N-acetylgluco

167 Dolichol phosphate, synthesized from the mevalonate path

168 .75 M NaCl) salt, as was the glycan bound to dolichol phosphate, the lipid upon which the N-linked gl

169 tical protein and regions with similarity to dolichol phosphate-D-mannose:protein O-D-mannosyltransfe

170 Archaea and eukaryotes share a dolichol phosphate-dependent system for protein N-glycos

171 responsible for the transfer of mannose from dolichol phosphate-mannose (Dol-P-Man) to serine/threoni

172 GlcNAc and non-competitive inhibition toward dolichol phosphate.

173 ive toward UDP-GlcNAc and competitive toward dolichol phosphate.

174 Dolichol-phosphate mannose (Dol-P-Man) is a key mannosyl

175 ases such as nucleotide-activated sugars and dolichol-phosphate sugars.

176 patients were approximately 95% deficient in dolichol-phosphate-mannose (Dol-P-Man) synthase activity

177 ntified as a small stabilizer subunit of the dolichol-phosphate-mannose (DPM) synthase complex.

178 mutations in DPM2, 1 of the subunits of the dolichol-phosphate-mannose (DPM) synthase; the patient i

179 In Archaea, dolichol phosphates have been implicated as glycan carri

180 olcanii contains a series of C(55) and C(60) dolichol phosphates presenting saturated isoprene subuni

181 Dolichol plays an indispensable role in the N-glycosylat

182 5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) h

183 nzyme that catalyzes the reaction: GDP-Man + dolichol-PP-GlcNAc2 --> dolichol-PP-GlcNAc2-Man + GDP.

184 reaction: GDP-Man + dolichol-PP-GlcNAc2 --> dolichol-PP-GlcNAc2-Man + GDP.

185 Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Tricho

186 s (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3.

187 ases, this inventory accurately predicts the dolichol-PP-glycans observed.

188 to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many

189 2 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorde

190 the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from second

191 A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexu

192 Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face

193 e alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked mon

194 2)-P-P-dolichol or Man(9)[(3)H]GlcNAc(2)-P-P-dolichol, respectively.

195 All four major dolichol species-dolichol-17 (Dol-17), Dol-18, Dol-19, a

196 CPTBP in yeast and in E. coli confirmed that dolichol synthase activity strictly requires both protei

197 n by GlcNAc-1-P transferase (GPT), mannose-P-dolichol synthase, glucose-P-dolichol synthase, or LLO s

198 GPT), mannose-P-dolichol synthase, glucose-P-dolichol synthase, or LLO synthesis in vitro, as reporte

199 r work therefore identifies the basis of the dolichol synthesis defect in Chinese hamster ovary Lec5

200 We recently found that dolichol synthesis from polyprenol occurs in three steps

201 he initial steps of Glc(3)Man(9)GlcNAc(2)-PP-dolichol synthesis generate the lipid intermediate Man(5

202 This led us to investigate defective dolichol synthesis in Lec5 and Lec9 cells.

203 cis-prenyltransferase (CPT) is required for dolichol synthesis, but also point to other factor(s) th

204 S is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosyla

205 zyme responsible for synthesis of GlcNAc-P-P-dolichol, the committed step of dolichol-P-P-oligosaccha

206 l) stimulated the biosynthesis of GlcNAc-P-P-dolichol; the apparent K(i) values for GlcNAc-P-P-dolich

207 ctivity in vitro and convert Man5GlcNAc2-P-P-dolichol to Glc0-3Man9GlcNAc2-P-P-dolichol in vivo.

208 dicated competitive inhibition by GlcNAc-P-P-dolichol toward the substrate UDP-GlcNAc and non-competi

209 nt N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-s

210 ve N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B.

211 feed into biosynthetic pathways for sterols, dolichol, ubiquinone, heme, isopentenyl adenine, and pre

212 hosphate, an important precursor of sterols, dolichols, ubiquinones, and prenylated proteins.

213 or GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol under basal conditions were 4.4 and 2.8 microM,

214 ides (LLO; glucose(3)mannose(9)GlcNAc(2)-P-P-dolichol) used for protein N-glycosylation.

215 terized, and the human Lec35 gene (mannose-P-dolichol utilization defect 1) was mapped to 17p12-13.

216 Inhibition by GlcNAc-GlcNAc-P-P-dolichol was uncompetitive toward UDP-GlcNAc and competi

217 or GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol were 2.2 and 11 microM, respectively.

218 lls because statin prevents the synthesis of dolichol, which is essential for the formation of dolich

219 ular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endoso

220 onstrated abundant Glc(3)Man(9)GlcNAc(2)-P-P-dolichol, without hypoglycosylation, CDG-Ia fibroblasts